Preliminary Analysis of Placental Metabolome in Maternal Obesity

Introduction: Maternal obesity is associated with a lipotoxic placental environment that may directly affect placental function and metabolism. Metabolomics is increasingly applied in maternal-fetal medicine for its clinical potential, by identifying specific metabolic profiles, mostly in bio-fluids such as blood, urine or amniotic fluid. This is the first preliminary study analyzing placental metabolomics in normal weight and obese pregnancies. Methods: Placentas at term were collected, washed and immediately frozen in liquid nitrogen at elective cesarean section from 20 normalweight (NW: BMI 18-25 kg/m2) and 18 obese (OB: BMI more than 30 kg/m2) women. Metabolites extraction method was optimized for hydrophilic and lipophilic phases, then analyzed by GC-MS. PLS-DA multivariate statistical analysis was applied. Results: Gestational age, fetal and placental weights were not significantly different between OB and NW.Lipophilic phase analysis in OB showed significantly lower levels of stearic acid and of the LC-PUFA derivatives DHA and arachidonic acid. Hydrophilic phase analysis revealed several metabolites allowing PLS-DA discrimination of data with significantly different levels in OB vs NW: increased glycerol, uracile, hypoxanthine, purine derivative, nicotinamide, glucose-6-P, 3-phosphoglycerate, tyrosine, isoleucine, phenylalanine, leucine, serine; decreased lysine, taurine, inosine, aspartic acid, inositol, gluconic acid, guanosine, glutamine. Conclusion: To our knowledge, this is the first study providing preliminary data on a broad range of metabolites in human obese placentas. Placental metabolome of OB showed a specific fatty acids profile suggesting a disruption of LC-PUFA biomagnification. Moreover, many of the altered metabolites in OB are part of metabolic pathways involved in antioxidant defenses and nucleotide production, as well as energy production and lipid synthesis, supporting a shift towards higher placental metabolism. Metabolic signatures in obese placentas may thus reflect changes occurring in the intrauterine metabolic environment, which may have effect on the development of adult diseases. This study can lay the foundation to further metabolomics placental characterization in the context of obesity. It can represent an additional missing link combining the two separated biological compartments of maternal blood and amniotic fluid, already investigated in other studies. Moreover, future works based on these preliminary data will help identifying a specific placental phenotype of obese pregnancies.